Cardiorenal effects of lidocaine and procaine amide in the conscious dog

1975 ◽  
Vol 228 (5) ◽  
pp. 1440-1445 ◽  
Author(s):  
WJ Mandel ◽  
MM Laks ◽  
AI Arieff ◽  
K Obayashi ◽  
H Hayakawa ◽  
...  

Simultaneous measurements of hemodynamics, arterioventricular (AV) conduction, and renal functioner were obtained in conscious dogs. Catheters were implanted for the long-term measurement of central aortic, right ventricular, and pulmonary artery pressure. AV conduction was assessed following surgical implantation of multipolar electrode plaques in the area of the bundle of His, as well as on the epicardium of the right and left atria and ventricles. Renal function was assessed utilizing standard techniques. Following control measurements, lidocaine, 1 mg/kg, or procaine amide, 10 mg/kg, was administered intravenously. Subsequently, serial measurements were obtained for a 90-min period. No significant changes in hemodynamics were observed following either drug. Procaine amide produced a significant increase in heart rate and a minimal increase in QRS duration associated with a decrease in low right atrial to His bundle conduction time. However, no significant changes in cardiac conduction were observed after lidocaine administration. Renal function was unaffected by lidocaine but significantly depressed by procaine amide, as demonstrated by a decrease in GFR and effective renal flow. In summary, acute administration of procaine amide significantly alters renal function in the conscious dog with minimal effects on AV conduction and hemodynamics.

1994 ◽  
Vol 266 (3) ◽  
pp. H861-H866 ◽  
Author(s):  
Y. Inoue ◽  
Y. Furukawa ◽  
H. Nakano ◽  
S. Sawaki ◽  
T. Oguchi ◽  
...  

We investigated whether the intracardiac parasympathetic ganglia for sinoatrial (SA) nodal pacemaker cells control the right atrial contractility selectively and totally in the autonomically decentralized heart of the open-chest anesthetized dog. Stimulation of the intracardiac parasympathetic nerves to the SA nodal area (SAP Stim) decreased the right atrial pressure (a wave pressure) and its first pressure derivative (dP/dt) as well as the atrial rate but did not change the atrioventricular (AV) conduction time. Stimulation of right and left cervical vagosympathetic complexes (CV Stim) decreased the a wave pressure, dP/dt, and atrial rate and prolonged the AV conduction time. When SAP and CV Stim decreased the atrial rate similarly, the decreases in a wave pressure and dP/dt in response to SAP Stim were less than those to CV Stim in unpaced and paced hearts. When treatment with hexamethonium bromide or tetrodotoxin into the SAP Stim locus abolished the decreases in atrial rate evoked by SAP and CV Stim, each treatment abolished the decrease in a wave pressure response to SAP Stim but only slightly attenuated the pressure response to CV Stim. These results demonstrate that right atrial pressure is modified by efferent parasympathetic neurons, which are located in a region that differs from that of efferent parasympathetic neurons controlling heart rate.


1983 ◽  
Vol 244 (2) ◽  
pp. R235-R243
Author(s):  
J. M. Goldberg ◽  
M. H. Johnson ◽  
K. D. Whitelaw

The effects of supramaximal stimulation of the right and left cervical vagi on heart rate, pacemaker localization, and atrioventricular (AV) conduction were investigated in 15 anesthetized open-chest chickens before and after atropine sulfate. Epicardial bipolar electrograms were recorded from selected atrial sites and right ventricle. A back lead electrocardiogram was also recorded. The effect of stimulation on atrioventricular conduction was evaluated during pacing from one of the right atrial recording sites. Supramaximal stimulation of either cervical vagus produced bradycardia but not cardiac arrest. Heart rate was reduced from an average spontaneous rate of 282 +/- 13 (SE)/min to 161 +/- 13/min with stimulation of the right and left cervical vagus. Pacemaker shifts occurred in over 50% of the vagal stimulations. The most frequent shift occurred to the lower AV node or ventricles. Pacemaker shifts to the AV junctional region producing almost simultaneous activation of the atria and ventricles were not observed. Vagal stimulation during atrial pacing produced minimal prolongation in AV conduction time [right vagus, 13 +/- 3 (SE) ms; left vagus, 8 +/- 2 ms]. Second and third degree heart blocks were not observed during pacing. Vagal stimulation after atropine indicates that the cervical vagi do not contain sympathetic fibers going to pacemaker or AV conduction tissues.


2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
A Reddy ◽  
S L Nethercott ◽  
W Teh ◽  
E M D De Bie ◽  
J Pepke-Zaba ◽  
...  

Abstract Background Although bradycardia-related sudden death is common in patients with idiopathic pulmonary arterial hypertension (IPAH), the prevalence and prognostic significance of atrioventricular (AV) conduction disease in this patient group is not well-established. Objectives – Determine the prevalence of AV conduction disorders in patients with IPAH – Investigate the relationship between AV block and functional outcomes and mortality. Method 12-lead electrocardiograms (ECGs) of patients with IPAH were analysed. Patients were categorised according to the presence or absence of AV block. Demographic, pulmonary haemodynamic, cardiac structural characteristics and expression of genes associated with cardiac conduction were compared and functional and mortality outcomes analysed between groups. Student's t-tests and χ2 tests were used to compare data. Survival was estimated using Kaplan-Meier analyses. Initial exploratory covariates were included in a univariate analysis and those terms with P-value of <0.1 were then used to generate a Cox proportional-hazards multivariate model. Results 135 IPAH patients (mean age 55±16 years, 28.1% male) were eligible for analysis. Median follow up was 9 years (interquartile range 4–14 years). AV block was seen in 34.8% of patients with IPAH compared to 10.8% of matched comparators (p<0.001), drawn from patients attending hospital for non-PAH related reasons. IPAH patients with conduction disease were more likely to be older (59±16 vs 53±17 years, p=0.038). AV block was associated with more severe right ventricular (RV) basal dilatation (5.1±1.0 vs 4.3±0.7cm, p=0.013) and worse RV function (fractional area change 26±9% vs 31±9%, p=0.14). Pulmonary haemodynamics, right atrial size and resting and exertional oxygen saturations were not significantly different. Expression of HCN1, HCN2, SCN1B, SCN5A, CAV1, and KCN2 genes in peripheral blood from a subcohort was similar between those with and without AV block. Lower 6 minute walk distances (344±153 vs 408±140m, p=0.035) and worse CAMPHOR scores across all 3 domains were seen in those with AV block (figure 1), and mortality was significantly higher (36.2 vs 13.6%, p=0.002) (figure 2). On multivariate analysis the presence of bundle branch block (BBB) was independently associated with a 2.1-fold increased risk of death (95% CI 1.89–4.85, p=0.045). Conclusions AV conduction disorders are more prevalent in IPAH than the general population, and are associated with worse prognosis and functional status. Prospective study is required to validate this finding. In our cohort AV block could not be explained by hypoxia, differences in pulmonary haemodynamics nor, in a small subgroup, by differential expression of specific transmembrane ion channels implicated in cardiac conduction. More detailed investigation into causal mechanisms of AV block in IPAH could establish whether improved prognosis could be achieved by treatment of AV block. FUNDunding Acknowledgement Type of funding sources: None. Figure 1 Figure 2


1997 ◽  
Vol 25 (6) ◽  
pp. 615-620 ◽  
Author(s):  
M. Tanaka ◽  
T. Nishikawa

Twenty-seven halothane-anaesthetized, mechanically ventilated adult mongrel dogs were randomly assigned to either respiratory acidosis group [pHa 7.22 (0.03, SD), PaCO2 9.6 (1.1) kPa, base excess –0.5 (1.4) mmol.l–1, n=9], metabolic acidosis group [pHa 7.20 (0.05), PaCO2 5.5 (0.4) kPa, base excess –11.1 (2.1) mmol.l–1, n=9], or non-acidosis group [pHa 7.37 (0.07), PaCO2 5.2 (0.4) kPa, base excess –1.1 (1.5) mmol.l–1, n=9]. Respiratory acidosis and metabolic acidosis were induced by decreasing respiratory rate and continuous infusion of 2 mmol.l–1 hydrochloric acid, respectively. Sodium bicarbonate solution 1 mmol.kg–1 was injected into the right atrium over five seconds when haemodynamic stability was obtained. In all three groups, acute administration of sodium bicarbonate produced transient decreases in mean arterial pressure and RV dP/dtmax, and transient increase in right atrial pressure 30 seconds after injections, but these variables returned to the pre-injection values by the end of the three minutes observation period. Although no significant differences were seen in haemodynamic variables among the three groups at 30 seconds, one and three minutes, maximum reductions in both RV dP/dtmax and PBF in the metabolic acidosis group (260 (143) mmHg.s–1 and 0.38 (0.26) l.min–1) were significantly greater than those in the non-acidosis group (127 (34) mmHg.s–1 and 0.08 (0.09) l.min–1; P<0.05).


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Martinez Cossiani ◽  
S Castrejon ◽  
C Escobar ◽  
M Ortega ◽  
M Batlle ◽  
...  

Abstract Introduction re-entry mechanisms around mitral and tricuspid annuli are frequent causes of left and right atrial flutter (AFt) respectively in patients with ipsilateral atrial pathology. However, clinical and electrophysiological characteristics of other types of atrial re-entries that could involve both AV annuli are less known. Purpose characterize biannular atrial flutters. Methods 4 patients with AFt were submitted for ablation (aged 30, 31, 58 and 61 yo; 2 females). All had a cardiac congenital disease with a prior surgical procedure: 3 atrial septal defects (ASD) with surgical repair and 1 with transposition of the great arteries (TGA) with Senning repair. The AFt had a cycle length (CL) of 290, 315, 330 y 340 ms respectively and 1:1 AV conduction in 3 of them. For the electrophysiological study, a multipolar catheter (20 or 24 poles) was placed in the right atrium (RA) in every patient, showing counterclockwise and clockwise activation in 1 and 3 patients, respectively. Coronary sinus (CS) activation was proximal to distal in one patient and distal to proximal in the other 2. No CS activation could be obtained in the patient with Senning repair. Results each AFt was mapped by entrainment from different sites of the RA, showing post-pacing intervals (PPI) similar to the CL of the AFt around the tricuspid annulus in all of them and also from proximal and distal CS in the 3 patients with ASD. Access to the native left atrium (LA) was achieved in the patient with Senning repair, showing PPIs around the mitral annulus that were similar to the LC of the tachycardia. In 2 patients the attempt to get to the LA through the interatrial septum (IAS) could not be achieved and was unattempted in the other one. Recordings and PPIs of the LA roof were obtained from the right branch of the pulmonary artery in 2 patients. Counterclockwise AFt and clockwise AFt by single biannular perimitrotricuspid rotation in 1 and 3 patients respectively. The AFt was ended and no reinduction was possible after radiofrequency application that achieved cavotricuspid isthmus block in all of the patients. Conclusions reentry around both AV annuli is possible as a single loop, counterclockwise or clockwise, of simultaneous rotation as a clinical mechanism of Aft. This type of AFt seems to be associated to absence or severe damage in the IAS.


1990 ◽  
Vol 258 (1) ◽  
pp. H38-H44 ◽  
Author(s):  
A. S. Pickoff ◽  
A. Stolfi

The effects of tonic right and left vagal stimulation (RVS and LVS) on electrophysiological properties of the immature myocardium and specialized conduction system were evaluated in 11 neonatal canines pretreated with propranolol (1 mg/kg iv). Electrophysiological studies were performed by recording intracardiac electrograms from multiple endocardial catheters during programmed electrical stimulation. Assessments were made of sinus node function, intra-atrial, atrioventricular (AV) nodal and His-Purkinje conduction, and atrial and ventricular refractoriness in the control state and during RVS and LVS at 4–12 Hz. Vagal stimulation prolonged the sinus cycle length; RVS produced a 38% increase and LVS a 25% increase at 8 Hz (P less than 0.01). There were no changes in the intra-atrial or His-Purkinje conduction times. Comparable increases occurred during RVS and LVS in the paced cycle length resulting in AV nodal Wenckebach, the AV nodal conduction time at a paced cycle length of 340 ms, and the effective and functional refractory periods of the AV node, suggesting symmetrical influences of the right and left vagus on neonatal AV nodal function. Right atrial effective and functional refractory periods shortened significantly during vagal stimulation (ERP, 36% RVS and 23% LVS; FRP, 27% RVS and 15% LVS), and in 5 of 11 neonates, a sustained regular atrial tachyarrhythmia was induced during atrial extra-stimulation. Small yet significant increases were observed in the right ventricular ERP and FRP during vagal stimulation. This study provides information regarding the functional integrity of the parasympathetic nervous system and its potential role as a modulator of the electrophysiological properties of the newborn heart.(ABSTRACT TRUNCATED AT 250 WORDS)


1975 ◽  
Vol 38 (5) ◽  
pp. 934-936 ◽  
Author(s):  
J. Beazell ◽  
D. Garner ◽  
M. M. Laks

A method is presented for a relatively simple nontraumatic chronic left heart catheter preparation for the study of left ventricular hemodynamics in the conscious dog. In 30 dogs an 8 Fr Cordis catheter was modified and implanted into the left ventricle via the right atrial septum. Transseptal catheterization was performed without significant morbidity and mortality. Left ventricular cineangiograms and pressures and cardiac outputs have been repeatedly performed on fully conscious dogs with no apparent discomfort displayed by the dog.


1997 ◽  
Vol 272 (5) ◽  
pp. H2289-H2298 ◽  
Author(s):  
D. A. Igel ◽  
D. W. Wallick ◽  
P. J. Martin ◽  
M. N. Levy

We tested the hypothesis that the effect of phasic vagal stimulation on atrioventricular (AV) conduction time is affected by the site of atrial pacing in anesthetized dogs. We paced the right atrium at a constant cycle length from the interatrial septum (IAS), superior coronary sinus (SCS), or inferior coronary sinus (ICS) regions, and we evaluated the time-dependent effects of vagal stimulation on AV conduction at each pacing site. When we stimulated the vagi at stimulus (St)-A phases greater than 136 +/- 40 ms and less than the phase that blocked AV conduction (182 +/- 70 ms), IAS pacing prolonged A-V intervals by 8.6 +/- 8.2 ms more than ICS pacing. A change in pacing site affected the A-V intervals by up to 30 ms when we stimulated the vagus at those times that caused the A-V intervals to prolong maximally. Furthermore, the effect of atrial pacing site on A-V intervals was modulated by AV nodal recovery times during the second or third cycles after the vagal stimulus.


EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
M Toniolo ◽  
L Rebellato ◽  
D Muser ◽  
E Daleffe ◽  
A Proclemer ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Focal atrial tachycardias (ATs) can arise from several different anatomic regions both in the right atrium (RA) and left atrium (LA). The prevalence of focal atrial tachycardia is not well known. A European study of young males applying for pilot licenses demonstrated that 0.34% had asymptomatic atrial tachycardia and 0.46% had symptomatic atrial tachycardia1. It is well-recognized that these foci do not occur randomly throughout the atria but tend to cluster at characteristic anatomic locations. However, the distribution of these sites in the total amount of ATs is not well recognized. Purpose The objective of this study was to determine the prevalence of different anatomic locations of ATs in the electrophysiology lab of a single large center (300 ablations per year) and to verify the site of ablation. Methods We collected 150 consecutive patients submitted to catheter ablation of ATs between January 2010 to December 2020. Anatomic localization of the atrial focus was performed during tachicardia by analysis of endocardial activation sequence. Results The distribution of the different anatomic locations is rappresented in the figure. In 134 patients (89%) ATs were localized in the RA. In the RA, these foci mainly occured along the crista terminalis (32%), the perinodal region (22,6%), the anterior right sided septum, near the foramen ovale (9,3%), the posterior right-sided septum (8%), the ostium of the coronary sinus (5,3%), the tricuspid annulus (5,3%), the superior vena cava (4,6%), the infero-lateral wall (2,5%), the right atrial appendage (0,6%) and the cavotricuspid histhmus (0,6%). In the LA (11%), foci occur predominantly at the pulmonary vein ostia (5,2%) and less commonly at the mitral annulus (2,5%), the left sided septum (0,6%), the appendage ridge (0,6%), the roof (0,6%) and the anterior wall (0,6%). For each location of AT, the ablation was performed at the earliest activation site, but about the perinodal ATs, the ablation was performed at the non coronary sinus of Valsalva of the aortic root, regardless the earliest activation site, for avoiding to create damages to the atrio-ventricular (AV) conduction system. Conclusions ATs mainly arise from the RA. Crista terminalis is the most common site but the perinodal region is the second more frequent site. The ablation of ATs from the perinodal region is challenging for the risk of damages to the AV conduction system. The relatively low prevalence of ATs arising from the pulmonary veins could be explained for the likely degeneration of these ATs in atrial fibrillation. Abstract Figure.


Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Eric I Rossman ◽  
Kun Liu ◽  
Gwen A Morgan ◽  
Robert E Swillo ◽  
John Butera ◽  
...  

Atrial fibrillation (AF) and atrial flutter (AFL), the most common sustained cardiac arrhythmias, are major contributors to cardiovascular morbidity and mortality in the adult population. Current pharmacologic treatment of AF/AFL is only moderately successful and not well tolerated among patients, highlighting an unmet medical need for safer, effective agents. GAP-134 is the first small molecule gap junction modifier developed for the prevention of AF/AFL. In preliminary experiments, this modified antiarrhythmic dipeptide with similar activity to the antiarrhythmic hexapeptide rotigaptide, significantly prevented conduction velocity slowing in rat atrial strips subjected to metabolic stress at 10 nM (5.6±9.4%) and 100 nM (0.4±5.0%) compared to controls (−29.1±5.3%). In the canine sterile pericarditis model, conduction time (CT, n=5) and AF/AFL inducibility (n=9) were measured 2–3 days post-operatively in closed chest studies, using electrodes placed at the right atrial appendage (RAA), the Bachmann’s bundle (BB), and the posterior left atrium (LA). CT, measured between the BB and LA, was significantly faster after GAP-134 infusion (average plasma concentration was 73.1 ng/ml) at RAA pacing rates of 200 bpm (66.2±1.0 ms vs 62.0±1.0 ms; p=2.49E-08), 300 bpm (64.4±0.9 ms vs 61.0±1.3 ms; p=2.67E-03), and 400 bpm (67.2±1.6 ms vs 65.0±1.9 ms; p=0.041). Induction of AF/AFL was attempted using a burst pacing protocol, at all three atrial sites, starting at 500 bpm and increasing at increments of 20 bpm until 800 bpm. The average number of successful AF/AFL inductions per animal was significantly decreased after GAP-134 infusion (2.7±0.6 vs 1.6±0.8; p=0.021), with the total number of inductions being decreased from 24 to 14. Mean AF/AFL duration per induction (603±119 s vs 260±116 s; p=0.021) and mean AF/AFL duration per animal (1364±419 s vs 705±483 s; p=0.049) were also significantly decreased after GAP-134 infusion, with total AF/AFL burden being decreased from 12280 s to 6348 s. In conclusion, GAP-134 shows consistent efficacy on measures of conduction and AF/AFL inducibility in the canine sterile pericarditis model. These findings, along with its oral bioavailability, underscore its potential as a highly effective atrial antiarrhythmic compound.


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